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    <div class="pagetitle">Welcome to SystemsInfluenza.org</div>

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        <h4>Program Goals & Technical Approach</h4>
        The aim of the Systems Influenza program is to provide new insights and understanding into how the immune system responds to and interacts with the influenza virus.  It is well known that different strains of the flu can have wildly different impacts on the population.  For instance, the H5N1 bird flu is highly virulent, with a mortality rate of about 60% of the known cases in humans; however, it has thus far been only marginally transmissible from person to person.  Conversely, the 2009 H1N1 pandemic strain displayed remarkable transmissibility, sweeping through the global population, but causing relatively mild disease, similar to previously circulating seasonal strains.  Here, we are applying Systems Biology techniques to unravel the complex host-pathogen interactions that lead to these tremendously divergent outcomes.
        <br/><br/>
        Our approach to these studies -and the unifying theme to Systems Influenza projects- is to compare the innate immune response to low- and high-pathogenicity infections and develop an integrated model for the viral and host factors that contribute to virulence.  Integrated models are derived by combining information from a number of “omics” technologies, such as transcriptomics, proteomics, and lipidomics datasets.  Two model systems for influenza infection form the basis for the bulk of the research:  (1) in vitro infection of differentiated cultures of primary airway epithelial cells (human, mouse, swine) and (2) in vivo infection of mice.
        <br/><br/>
        Another major component of the Systems Influenza program is the use of proteomic approaches to identify novel interactions between viral and host proteins and gain insight into host defense and viral evasion mechanisms.  We are also employing high-throughput lipidomic technologies to determine whether the composition of the viral envelope correlates with pathogenicity and to measure the changes in the lipid content of host cells following infection.  Finally, we are using the approaches described above to characterize the regulatory networks underlying the host response to secondary infection by S. aureus following a primary influenza infection.
        <br/><br/>

        <h4>Program History & Participants</h4>
        Work for this program is conducted under a contract awarded by the National Institute for Allergy and Infectious Diseases (NIAID, a division of the National Institutes of Health).  More information about this contract, as well as other components of NIAID's broader research program, is available at our sponsor's website, <a href="http://www3.niaid.nih.gov/research/resources/sb/">Systems Biology for Infectious Diseases Research</a>.  The contract was awarded in 2008 to Principal Investigator Dr. Alan Aderem at the Institute for Systems Biology (ISB) in Seattle, Washington.  Dr. Aderem continues to lead the program from Seattle BioMed, where he assumed the role of President starting in 2012.  Dr. John Aitchison joined as Co-PI in 2011 and shares administrative duties with Dr. Aderem.  Under their direction, the various objectives of the research program are carried out through collaborations amongst six research institutions:
        <br/><br/>

        <h4>Institute for Systems Biology (ISB)</h4>
        <dl>
          <dt><a href="http://www.systemsbiology.org/aitchison-group" target="_blank">John Aitchison, Ph.D.</a></dt>
          <dd><i>Co-Principal Investigator</i><br/>Dr. Aitchison oversees all genomics and proteomics work conducted at ISB's core facilities in addition to program administration at ISB.</dd>
          <dt><a href="http://www.systemsbiology.org/shmulevich-group" target="_blank">Ilya Shmulevich, Ph.D.</a></dt>
          <dd><i>Co-Investigator</i><br/>Dr. Shmulevich directs the Computational Core at ISB, which coordinates data management, dissemination, and maintains the SystemsInfluenza.org web portal.</dd>
        </dl>

        <h4>Seattle Biomedical Research Institute (Seattle BioMed)</h4>
        <dl>
          <dt><a href="http://seattlebiomed.org/bio/aderem" target="_blank">Alan Aderem, Ph.D.</a></dt>
          <dd><i>Principal Investigator</i><br/>Dr. Aderem directs the Functional Genomics and Proteomics Cores.  Samples for both of these analytical cores are generated from experiments conducted by the Pathophysiology Core, both at St. Jude Children's Hospital (below) and Seattle BioMed.</dd>
        </dl>

        <h4>St. Jude Children's Research Hospital</h4>
        <dl>
          <dt><a href="http://www.stjude.org/stjude/v/index.jsp?vgnextoid=e5dd10e88ce70110VgnVCM1000001e0215acRCRD&vgnextchannel=a0d513c016118010VgnVCM1000000e2015acRCRD" target="_blank">Peter Doherty, Ph.D.</a></dt>
          <dd><i>Co-Investigator</i><br/>Dr. Doherty oversees the Pathophysiology Core, which conducts much of the <i>in vivo</i> and <i>in vitro</i> mouse experiments.</dd>
          <dt><a href="http://www.stjude.org/webby" target="_blank">Richard Webby, Ph.D.</a></dt>
          <dd><i>Co-Investigator</i><br/>Dr. Webby participates in oversight of the virology experiments.</dd>
        </dl>

        <h4>Seattle Children's Hospital Research Institute</h4>
        <dl>
          <dt><a href="http://www.seattlechildrens.org/medical-staff/Craig-E-Rubens/" target="_blank">Craig Rubens, M.D., Ph.D.</a></dt>
          <dd><i>Co-Investigator</i><br/>Dr. Rubens participated in the <i>S. aureus</i> superinfection studies produced by the Pathophysiology and Genomics Cores.</dd>
        </dl>

        <h4>University of California, San Diego</h4>
        <dl>
          <dt><a href="http://cobra.ucsd.edu/" target="_blank">Edward A. Dennis, Ph.D.</a></dt>
          <dd><i>Co-Investigator</i><br/>Dr. Dennis directs Lipidomics Core A, which determines changes in eicosanoids and other fatty acid metabolite levels in BAL fluid from influenza infected mice.</dd>
        </dl>

        <h4>Vanderbilt University, School of Medicine</h4>
        <dl>
          <dt><a href="http://www.alexbrownlab.org/" target="_blank">H. Alex Brown, Ph.D.</a></dt>
          <dd><i>Co-Investigator</i><br/>Dr. Brown directs Lipidomics Core B, which analyzes the lipid composition of the viral envelope and the membranes of infected cells.</dd>
        </dl>

        <br/>
        <h4>Contact Information</h4>
        <dl>
            <dt>Alan Aderem, Ph.D.</dt>
            <dd>Principal Investigator</dd>
            <dd><a href="mailto:alan.aderem@seattlebiomed.org" target="_blank">alan.aderem@seattlebiomed.org</a></dd>
            <dd>(206) 256-7200</dd>
        </dl>
        <dl>
            <dt>Drew Dover</dt>
            <dd>Program Manager</dd>
            <dd><a href="mailto:drew.dover@seattlebiomed.org" target="_blank">drew.dover@seattlebiomed.org</a></dd>
            <dd>(206) 256-7408</dd>
        </dl>
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